Celiac Disease

  • Model for autoimmune disease with environmental trigger
  • – Several wheat proteins is responsible for the grain’s toxicity in CD
  • –  Storage forms of wheat proteins: Prolamin, Glutenin, albumin, globulin
  • – Prolamin of wheat is referred to as ‘Gliadin’
  • – Grains that activate the disease: Wheat, rye, barley
  • Grains that do not activate the disease: Rice, corn (ভুট্টা), sorghum (যব), millet (জোয়ার)
  • – Oat (জই) is tolerated by almost CD patients
  • * Mean age at presentation 45 years
  • * 25% patients diagnosed after 60 years
  • * The length of small intestine involvement varies among patients and it depends upon severity of the disease
  • * When the whole length of the gut is not involved, the proximal intestine is severely involved
  • * Sparing of the proximal intestine with distal involvement may occur but it is uncommon

 

  • CLINICAL FEATURES OF CELIAC DISEASE:
  • GI features:
  • Diarrhoea, steatorrhoea, abdominal bloating, flatulence, wt.loss
  •                            Diarrhoea:
  •           –  Often episodic, rather than continuous
  •          – Nocturnal, early morning, post prandial diarrhea common
  •          – With extensive involvement >10 stool/day may occur
  •          – Steatorrhoea often absent with only proximal involvement
  •          – Vague abdominal discomfort, bloating similar to IBS
  • ** Because of the difficulty in distinguishing celiac disease with mild GI manifestation from symptomatic IBS, serologic testing of IgA, EMA or Ig tTG should be considered in diarrhea predominant IBS
  • ** Severe abdominal pain in celiac disease may occur in intussusception, ulcerative jejunitis and intestinal    lymphoma
  • Other important extraintestinal features:
  • Anemia: Due to impaired iron, folic acid absorption and Vit.B12 malabsorption in severe disease
  • Osteopenia: Due to impaired calcium absorption, Vit.D deficiency (due to impaired fat soluble vitamin. Intrluminal calcium and magnesium binds to unabsorbed dietary fatty acids
  • Neurological symptoms: Gluten ataxia, peripheral neuropathy, epilepsy
  • Gynecologic and fertility problems: Amenorrhea, delayed menarche, infertility
  • Male infertility: Due to low sperm count, impotence, malnutrition

               

  • Physical findings of CD:
  • Mild disease: Normal
  • Severe disease: Features of malabsorption
  •                                  – Emaciation
  •                                  – Weight Loss
  •                                  -Loose skin folds
  •                                  – Muscle wasting
  • Clubbing , koilonychias of fingers
  • Edema
  • Low grade fever with anemia- occasional
  • Peripheral lymphadenopathy if complicated by lymphoma
  • Skin manifestations
  •      – Increased skin pigmentation
  •      – Dermatitis herpetiformis
  •      – Spontaneous ecchymosis
  •     – Hyperkeratosis folicularis due to Vit. A deficiency
  •      – Pallor due to anemia
  • Examination of mouth:
  •           – Aphthous ulcer
  •           – Angular cheilosis
  •           – Glossitis
  •           – Dental enamel defect
  •                          Abdomen:
  •      – Doughy consistency (due to intestinal loop distention with gas and fluid)
  •        – Ascites (due to hypoproteinemia)
  •                          Extremity:
  •     -Loss of various sensory modality (touch, vibration, position due peripheral neuropathy and spinal cord                demyelination)
  •      – Diminished/absent deep tendon reflex if severe neuropathy
  •                         Others:
  •     – Chvostek/trousseau sign (due to calcium/magnesium deficiency)
  •     – Bone tenderness (due to osteoporosis)
  • Celiac crisis/Gliadin shock:
  • Life threatening syndrome in which children/adult with untreated celiac disease presents with profuse diarrhea,   metabolic disturbance, renal dysfunction and in some instances hemodynamic instability
  •  INVESTIGATIONS:

 

  • – Specific celiac serology (IgA EMA, IgA tTG, IgA/IgG DGP) and small intestinal biopsy are the most reliable diagnostic tests for celiac disease
  • – EMA (Endomysial Antibody)
  •       • Even low titre is very specific for CD
  •       • Used less commonly than tTG (due to more labor intensive, expansive, laboratory variations)
  • – tTG (Tissue Transglutaminase Antibody)
  •         • In the setting of a normal biopsy it might indicate potential CD
  •         • False positive result is unlikely
  • – DGP (Deamidated Gliadin antibody)/ AGA(Anti gliadin antibody
  •          • Done to confirm or exclude CD in persons who have small bowel biopsy consistent with CD but a negative IgA tTG ( in case of IgA deficiency DGP can be used)
  • – Genetic testing for HLA DQ2/DQ8
  •          • Done in patients who is already adhering to GFD and with negative celiac serologies but without prior diagnostic serology or histopathology
  •                            Endoscopic findings of celiac disease:
  •                                     – Scalloping of mucosal folds
  •                                     – Flattening of duodenal folds
  •                                     – Nodularity and multiple fissures leading to mosaic-like appearance
  •                             Other causes of scalloping appearance
  •                                   – Eosinophilic gastroenteritis
  •                                    – Giardiasis
  •                                    – Amyloidosis
  •                                    – Tropical sprue
  •                                    – HIV enteropathy
  •                                                                
  •    Figure: Endoscopic finding of Celiac Disease

 

  • – Small intestinal Biopsy for the diagnosis of celiac disease
    • • Total 6-8 biopsy from 2nd and 3rd part of duodenum should be taken to diagnose celiac disease
    • • Biopsy from duodenal bulb increase the sensitivity
  •                                           Histology of Celiac disease:
  •                             – Mainly affects the mucosa of the small intestine
  •                             – Submucosa, muscularis propria and serosa are not involved
  •                             – Flat mucosal surface with complete absence of normal intestinal villi in severely affected patient
  •                             – Villous shortening
  •                            – Crypt hyperplasia (marked elongation of intestinal crypt
  •                            – Increased IEL
  •                            Increased lamina propria cellularity
  •                                                   – Cellular infiltrate consists largely of plasma cell and lymphocytes
  •                                                  – PMN, eosinophil, mast cell may also infiltrate
  •                                                   – Columnar to cuboidal transformation of epithelial cell
  •          Increased IEL (Intra Epithelial Lymphocyte) may occur in following diseases
  •                                           –  Celiac disease
  •                                           – Tropical sprue
  •                                            – SIBO
  •                                            – Peptic duodenitis
  •                                            – Hp infection
  •                                             – NSAID
  •                                            –  Autoimmune disease

 

 

 

 

 

 

  • Other laboratory tests:
  • Blood:
  •    – Combined iron and folic acid deficiency is characteristics
  •    – Severe anemia is uncommon except in pregnancy and if present should raise the suspicion of complication of the disease
  •    – Features of hyposplenism: target cells, siderocyte, Heinz bodies, crenated RBC,Howel-jolly bodies
  •   –  Chronically elevated aminotransferase (1.5- 2 times normal values)
  • Stool:
  • – Steatorrhoea, watery or bulky, semi-formed, light or greyish, malodorous, greasy-appearing stool
  • – Microscopic evaluation of stool fat is done by sudan III or IV stain of stool after hydrolysis with glacial acetic acid

 

  • Radiology:
  • Barium x-ray (SBT):
  • – Dilatation of the small intestine
  • – Reversal of mucosal pattern
  • – Flattening of the jejunal folds
  • – Increased number of ileal folds (Jejunalisation of ileum)
  • – Loss of normal feathery mucosal patterrn of jejunum

           

Barium follow through demonstrating Mild dilatation and “jejunalization” of the ileum

Rapid transit time, with barium dilution and flocculations

 

  • Abdominal CT/MRI
  • – Splenic atrophy
  • – Ascites
  • – Mesenteric lymphadenopathy
  • – Cavitatingry lyphadenopathy
  • ** Mesenteric lymphadenopathy is common in active celiac disease and does not indicate a need for investigation to exclude lymphoma
  • Important disorders associated with celiac disease:
  • – Dermatitis herpetiformis
  • – DM type I
  • – Down syndrome
  • – Hypo/Hyperthyroidism
  • – IgA deficiency
  • – IBD
  • – Microscopic colitis
  • – RA
  • – sarcoidosis
  • – fibrosing alveolitis
  • – IgA nephropathy
  • – Recurrent pericarditis
  • ** Negative association : Type2 DM

             

  •              TREATMENT OF CELIAC DISEASE:
  •       
  • Key elements in the management of Celiac Disease
  • – Consultation with a skilled dietitian
  • – Education about the disease
  • – Lifelong adherence to a gluten-free diet
  • – Identification and treatment of nutritional deficiencies
  • – Access to an advocacy group
  • – Continuous long-term follow-up by a multidisciplinary team
  • Gluten free diet
  •         – After starting GFD – most patients improve within afew weeks
  •         – In many, substantial symptomatic improvement is noticed within 48 hours, although it can take weeks or months to achieve full clinical, serologic and histologic remission
  •         – Histologic resolution may take upto 2 year due to inadvertent gluten exposure
  • Dietary supplement :                     
  • Glucocorticoid:
  •             – Not indicated in the routine management of celiac disease.
  •             – Reserved for refractory celiac disease or for severely ill patients who present with acute celiac crisis manifested by severe diarrhea, dehydration, weight loss, acidosis, hypocalcemia, and hypoproteinemia
  • Monitoring of celiac disease patients:
  • 1st year of diagnosis:
  • -3-6 monthly: To evaluate
  •                –  Symptom response
  •                – Adherence to diet
  •                – Provide additional counselling
  •                – Education
  •                – Measure tTG/ DDGP Ab
  •                – Correction of nutritional deficiency
  • After 1 year: BMD
  • 2 year after dietary therapy: Repeat biopsy to evaluate healing but not mandatory
  • In case of NRCD : Biopsy may be repeated earlier

 

  •                           Non Responsive Celiac Disease (NRCD)
  • Persistence of symptoms, signs and laboratory abnormalities typical of celiac disease despite adherence to GFD 6-12 months.
  • Consider:
  • – Review primary diagnosis
  • – Inadvertent gluten ingestion (most common)
  • – Other food intolerance (lactose, Fructose)
  • – Microscopic colitis
  • – IBS
  •                                  Refractory Celiac Disease (RCD)
  • Persistent or recurrent symptoms and signs of malabsorption with small intestinal villous atrophy despite strict GFD for more than 12 months and in the absence of other disorder including lymphoma
  •                      Type I Refractory Celiac Disease:
  •  – Lymphocyte infiltration of the small intestinal mucosa, similar to that seen in untreated celiac disease
  •  – Treatment of Type I RCD:
  •  – Exclude inadvertent gluten exposure
  •  – Evaluate and treat nutritional deficiency
  •                          Type II Refractory Celiac Disease:
  • – CD3 positive intraepithelial T cells exhibit an abnormal immunophenotype with lack of expression of normal cell surface differentiation markers such as CD8
  • – Type II RCD has less favourable prognosis than Type I RCD
  • – Treatment of Type II RCD:
  • – Same as Type I RCD
  • – Severe cases may require parenteral nutrition
  •                              Ulcerative Jejunoilitis
  •                          – Complication of celiac disease
  •                          – Ulceration and stricture of small bowel
  •                         – Many patients ultimately diagnosed as lymphoma
  •                        Suspicion:
  •                           – CD patients not responding to GFD
  •                           – Wt. loss
  •                          – Abdominal pain
  •                           – Stricture may perforate
  •                     Diagnosis: Enteroscopy, Contrast study of small intestine, abdominal CT, capsule endoscopy, Laparotomy
  • Treatment: GFD, Surgery

 


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